Spectrum Pharmaceutecals Inc (SPPI)

[antihama]

JTO abstract on NSCLC exon 20 insertion mutations.

Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of Non-Small Cell Lung Cancer

DOI: https://doi.org/10.1016/j.jtho.2018.06.019

Abstract
Introduction
EGFR exon 20 insertions (EGFRex20ins) comprise an uncommon subset of EGFR activating alterations relatively insensitive to first and second-generation EGFR tyrosine kinase inhibitors (TKIs). However, recent early clinical data suggests these patients may benefit from newer generation EGFR-TKIs. Comprehensive genomic profiling (CGP) identifies a broad spectrum of EGFRex20ins and associated co-occurring genomic alterations (GA) present in non-small cell lung cancer (NSCLC)

Methods
Hybrid capture-based CGP was performed prospectively on 14,483 clinically annotated consecutive NSCLC specimens to a mean coverage depth of >650X for 236 or 315 cancer-related genes.

Results
Of 14,483 NSCLC cases, CGP identified 263 (1.8%) cases with EGFRex20ins, representing 12% (263/2,251) of cases with EGFR mutations. 64 unique EGFRex20ins were identified, most commonly D770_N771>ASVDN (21%) and N771_P772>SVDNP (20%). EGFR amplification occurred in 22% (57/263). The most common co-occurring GA effected TP53 (56%), CDKN2A (22%), CDKN2B (16%), NKX2-1 (14%) and RB1 (11%); co-occurring GA in other known lung cancer drivers were rare (5%). Average tumor mutational burden (TMB) was low (mean 4.3, range 0-40.3 mutations/Mb). Clinical outcomes to first- and second-generation EGFR TKIs were obtained for 5 patients and none responded.

Conclusion
In the largest series of EGFRex20ins NSCLC, diverse EGFRex20ins were detected in 12% of EGFR-mutant NSCLC, a higher frequency than previously reported in smaller single-institution studies. Clinical outcomes demonstrated lack of response to EGFR TKIs. TMB was low, consistent with non-smoking associated NSCLC. Comprehensive sequencing revealed increased proportion and wide variety of EGFRex20ins, representing a population of patients significant enough for focused efforts on effective interventions.
https://www.jto.org/article/S1556-0864(18)30770-6/fulltext

12%!! Is this double what JT has been saying i.e. 5.5%. If so I'd have to say OMG! And Sweet!! I'm pretty sure we're talking apples to apples since the paper alluded to this being higher than what was normally thought of as prevalent but will double check one of these days.